The development of non-toxic, immunospecific therapy for autoimmune disease is a major goal of this work. The project is based on the demonstration in experimental autoimmune encephalomyelitis (EAE) that it is possible to prevent or reverse paralytic disease with monoclonal antibodies (mAb) specific for the T cell receptor (TcR) V region or for the class II major histocompatibility complex (MHC) molecule that presents myelin basic protein (MBP). Further, it is possible to design non-immunogenic peptides that block the ability of encephalitogenic myelin fragments to bind to MHC. In this project further development of blocking peptides for treatment of EAE will be undertaken. Peptides that not only block MHC but do not bind TcR will be tested. Finally, molecular vaccination with V-DJ and V-J peptides from the TcR sequence of encephalitogenic T cells will be used to treat EAE. These approaches using therapeutic peptides could lead to the rational design of drugs for autoimmune disease.